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A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice.

ABSTRACT: Can limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.

SUBMITTER: Abrams MJ

PROVIDER: S-EPMC8782573 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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A conserved strategy for inducing appendage regeneration in moon jellyfish, <i>Drosophila</i>, and mice.

Abrams Michael J MJ Tan Fayth Hui FH Li Yutian Y Basinger Ty T Heithe Martin L ML Sarma Anish A Lee Iris T IT Condiotte Zevin J ZJ Raffiee Misha M Dabiri John O JO Gold David A DA Goentoro Lea L

eLife 20211207

Can limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish <i>Aurelia</i> was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regenera ...[more]

PMID: 34874003

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Project description:BackgroundAlthough regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs.ResultsThese studies identified a core group of 5 microRNAs (miRNAs) that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema-associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFβ receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5.ConclusionsOur extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation for future functional studies to examine the process of natural cellular reprogramming in an injury context.

Dataset Information

A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice.

Publications

A conserved strategy for inducing appendage regeneration in moon jellyfish, <i>Drosophila</i>, and mice.

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Dataset Information

A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice.

Publications

A conserved strategy for inducing appendage regeneration in moon jellyfish, &lt;i&gt;Drosophila&lt;/i&gt;, and mice.

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OmicsDI is part of the ELIXIR infrastructure

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A conserved strategy for inducing appendage regeneration in moon jellyfish, <i>Drosophila</i>, and mice.